ABSTRACT
An altered balance between effector and regulatory factors is supposed to sustain the tissue-damaging immune response in inflammatory bowel disease (IBD). We have recently shown that in IBD, there is a defective synthesis of the counter-regulatory cytokine, interleukin (IL)-25. In this study we investigated factors that control IL-25 production in the gut. IBD patients produced less IL-25 when compared with normal controls. Stimulation of normal intestinal explants with tumor necrosis factor-α (TNF-α), but not interferon-γ (IFN-γ) or IL-21, reduced IL-25 synthesis. Consistently, IL-25 production was enhanced by anti-TNF-α both in vitro and in vivo. Upregulation of IL-25 was also seen in normal colonic explants stimulated with transforming growth factor-ß1 (TGF-ß1). As in IBD, TGF-ß1 activity is abrogated by Smad7, we next assessed whether inhibition of Smad7 with an antisense oligonucleotide enhanced IL-25 expression. Knockdown of Smad7 was accompanied by an increase in IL-25 production. Data show that IL-25 production is differently regulated by TNF-α and TGF-ß1 in the human gut.
Subject(s)
Gene Expression Regulation , Interleukin-17/metabolism , Intestinal Mucosa/immunology , Transforming Growth Factor beta1/metabolism , Tumor Necrosis Factor-alpha/metabolism , Celiac Disease/immunology , Gene Expression Regulation/immunology , Gene Knockdown Techniques , Humans , Inflammatory Bowel Diseases/immunology , Interleukin-17/genetics , Smad7 Protein/genetics , Smad7 Protein/metabolismABSTRACT
We describe the case of a thoracoscopic approach to giant lymph node hyperplasia (Castleman's disease) located in the mediastinum. In our patient the initial diagnosis was substernal goiter, but at cervical exploration the mass was found not to be continuous with the thyroid. The mass was easily identified through a lateral thoracoscopic approach and carefully removed. The postoperative course was uneventful, and the patient was discharged home on the fifth postoperative day. Histopathology revealed the features of Castleman's disease, mixed type. The prevalence, location, and pathogenesis of giant lymph node hyperplasia are described, together with the histology and clinical signs. Our report is proposed as the first case of an endoscopic approach to giant lymph node hyperplasia, which could be the best surgical approach for a mediastinal location.
Subject(s)
Castleman Disease/diagnosis , Castleman Disease/surgery , Goiter/diagnosis , Thoracoscopy/methods , Adult , Diagnosis, Differential , Female , Humans , Prognosis , Treatment OutcomeABSTRACT
Among the late complications of high-dosage pelvic radiotherapy for cervical cancer, anorectal and bladder malignancies are sporadically reported in the literature. In this study the possible relationships of previous radiotherapy with late appearance of neoplasms are analyzed and in particular post-radiotherapy interval, dosage and type or irradiation to the cervical area. The mechanisms or neoplastic transformation or irradiated tissues are also studied. Three clinical cases or women irradiated in the past because or cervical cancer and recently treated at our surgical Division for the appearance or four new pelvic malignancies in the irradiated field (three rectal and one bladder cancer are presented. In conclusion, the possible cause-effect relationships between previous radiotherapy and subsequent appearance of neoplasms are analyzed as well as the potential therapeutical consequences or considering these women high-risk subjects. The usefulness or recruiting women with history or previous radiotherapy for cervical cancer in a strict follow-up program (ultrasonography, cytology and endoscopy) is suggested in order to make an early diagnosis of the new pelvic malignancy with a better possibility or treatment.
